1. Eleven charts: 20th century dietary changes
2. The most important thing you probably don’t know about cholesterol
3. The Questionable Link Between Saturated Fat and Heart Disease
4. High Cholesterol And Heart Disease — Myth or Truth?
5. Web Tool to Check Heart Risk Is Doubted
6. Framingham Slides
7.
Lipid researcher, 98, reports on the causes of heart disease
8.
Foods High in Cholesterol Could Save Your Health.
9. Lifespan


These 11 Charts Show Changes in Diet in the 20th Century

The modern diet is the main reason why people all over the world are fatter and sicker than ever before. Everywhere modern processed foods go, chronic diseases like obesity, type 2 diabetes and heart disease soon follow.

The studies are clear on this... when people abandon their traditional foods in favor of modern processed foods high in sugar, refined flour and vegetable oils, they get sick (1, 2, 3). Of course, there are many things that can contribute to these health problems, but changes in the diet are the most important factor.

Here are 11 graphs that show everything that is wrong with the modern diet.

1. Total Sugar Intake Has Skyrocketed in The Past 160 Years

People in Western countries are consuming massive amounts of refined sugars, reaching about 150 lbs (67 kg) per year in some countries. This amounts to over 500calories of sugar per day.

The sources vary on the exact figures, but it is very clear that we are consuming way more sugar than our bodies are equipped to handle (4). Controlled human studies show that large amounts of sugar can lead to severe metabolic problems, including insulin resistance, metabolic syndrome, elevated cholesterol and triglycerides — to name a few (5, 6).

Added sugar is believed to be one of the main drivers of diseases like obesity, type 2 diabetes, heart disease and even cancer (7, 8, 9, 10).

2. Consumption of Soda and Fruit Juice Has Increased Dramatically

Of all the sugar sources in the diet, sugar-sweetened beverages are the worst. Fruit juice is actually no better... it contains a similar amount of sugar as most soft drinks (11).

Getting sugar in liquid form is particularly harmful. The studies show that the brain doesn't "register" liquid sugar calories the in the same way as calories from solid foods, which dramatically increases total calorie intake (12, 13). One study found that in children, each daily serving of sugar-sweetened beverages is linked to a 60% increased risk of obesity (14)..

3. Calorie Intake Has Gone up by Around 400 Calories Per Day

Although sources vary on the exact figures, it is clear that calorie intake has increased dramatically in the past few decades (15).

There are many complicated reasons for this, including increased processed food and sugar consumption, increased food availability, more aggressive marketing towards children, etc (16).

4. People Have Abandoned Traditional Fats in Favor of Processed Vegetable Oils

When health professionals started blaming saturated fat for heart disease, people abandoned traditional fats like butter, lard and coconut oil in favor of processed vegetable oils.

These oils are very high in Omega-6 fatty acids, which can contribute to inflammation and various problems when consumed in excess (17, 18). These oils are often hydrogenated, which makes them high in trans fats. Many studies have shown that these fats and oils actually increase the risk of heart disease, even if they aren't hydrogenated (19, 20, 21).

Therefore, the misguided advice to avoid saturated fat and choose vegetable oils instead may have actually fueled the heart disease epidemic.

5. People Replaced Heart-Healthy Butter With Trans-Fat Laden Margarine

consumption of butter and margarine in usa

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Another side effect of the "war" on saturated fat was an increase in margarine consumption.

Margarine was traditionally made with hydrogenated oils, which are high in trans fats. Many studies show that trans fats increase the risk of heart disease (22, 23).

Grass-fed butter actually contains nutrients that are protective against heart disease (like Vitamin K2), therefore the advice to replace heart-healthy butter with trans-fat laden margarine may have done a lot of damage (24).

6. Soybean Oil Has Become a Major Source of Calories

soybean oil consumption in usa

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The most commonly consumed vegetable oil in the U.S. is soybean oil. Soybean oil actually provided 7% of calories in the U.S. diet in the year 1999, which is huge (25)!

However, most people don't have a clue they're eating this much soybean oil. They're actually getting most of it from processed foods, which often have soybean oil added to them because it is cheap. The best way to avoid soybean oil (and other nasty ingredients) is to avoid processed foods.

7. Modern Wheat is Less Nutritious Than Older Varieties of Wheat

Wheat is a major part of the Western diet. It is found in all sorts of foods... breads, pastas, pastries, pizzas and various processed products.

However... wheat has changed in the past few decades.

Modern dwarf wheat was introduced around the year 1960, which contains 19-28% less of important minerals like Magnesium, Iron, Zinc and Copper. There is also evidence that modern wheat is much more harmful to celiac patients and people with gluten sensitivity, compared to older breeds like Einkorn wheat (26,27, 28).

Whereas wheat may have been relatively healthy back in the day, the same is not true of modern dwarf wheat.

8. Egg Consumption Has Gone Down

Eggs are among the most nutritious foods on the planet. Despite being high in cholesterol, eggs don't raise the bad cholesterol in the blood (29).

For some reason, the health authorities have recommended that we cut back on eggs, even though there is no evidence that they contribute to heart disease (30). Since the year 1950, we have decreased our consumption of this highly nutritious food from 375 to 250 eggs per year, a decrease of 33%.

This has contributed to a deficiency in important nutrients like Choline, which about 90% of Americans aren't getting enough of (31).

9. People Are Eating More Processed Foods Than Ever Before

This graph shows how consumption of fast foods has increased in the past few decades.

Keep in mind that even though it looks like people are still eating most of their foods "at home&" — this does not take into account the fact that most people are also eating processed, pre-packaged foods at home.

10. The Increased Vegetable Oil Consumption Has Changed The Fatty Acid Composition of Our Bodies

Most of the Omega-6 fats that people are eating is a fatty acid called linoleic acid.

Studies show that this fatty acid actually gets incorporated into our cell membranes and body fat stores. These fats are prone to oxidation, which damages molecules (like DNA) in the body and may be increasing our risk of cancer (32, 33, 34, 35, 36).

In other words, the increased consumption of processed vegetable oils has lead to actual harmful structural changes in our bodies. That's a scary thought.

11. The Low-Fat Dietary Guidelines Were Published Around The Same Time The Obesity Epidemic Started

The first dietary guidelines for Americans were published in the year 1977, almost at the exact same time the obesity epidemic started. Of course, this doesn't prove anything (correlation does not equal causation), but it makes sense that this could be more than just a mere coincidence.

The anti-fat message essentially put the blame on saturated fat and cholesterol (harmless), while giving sugar and refined carbs (very unhealthy) a free pass.

Since the guidelines were published, many massive studies have been conducted on the low-fat diet. It is no better at preventing heart disease, obesity or cancer than the standard Western diet, which is as unhealthy as a diet can get (37, 38, 39, 40).

For some very strange reason, we are still being advised to follow this type of diet, despite the studies showing it to be completely ineffective.



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The most important thing you probably don’t know about cholesterol

 


Summary:

Not all cholesterol is created equal

By now most people have been exposed to the idea of “good” and “bad” cholesterol. It’s yet another deeply ingrained cultural belief, such as the one I wrote about last week, that has been relentlessly driven into our heads for several decades.

But once we’ve put on our Healthy Skeptic goggles, which I know all of you fair readers have, we no longer simply believe what we’re told by the medical establishment or mainstream media. Nor are we impressed or in any way swayed by the number of people that tell us something is true. After all, as Anatole France said, “Even if fifty million people say a foolish thing, it is still a foolish thing.”

Words to live by.

The oversimplified view of HDL cholesterol as “good” and LDL cholesterol as “bad” is not only incomplete, it has also directly contributed to the continuing heart disease epidemic worldwide.

But before we discover why, we first have to address another common misconception. LDL and HDL are not cholesterol. We refer to them as cholesterol, but they aren’t. LDL (low density lipoprotein) and HDL (high density lipoprotein) are proteins that transport cholesterol through the blood. Cholesterol, like all fats, doesn’t dissolve in water (or blood) so it must be transported through the blood by these lipoproteins. The names LDL and HDL refer to the different types of lipoproteins that transport cholesterol.

In addition to cholesterol, lipoproteins carry three fat molecules (polyunsaturated, monounsaturated, saturated – otherwise known as a triglyceride). Cholesterol is a waxy fat particle that almost every cell in the body synthesizes, which should give you some clue about its importance for physiological function.

You do not have a cholesterol level in your blood, because there is no cholesterol in the blood. When we speak of our “cholesterol levels”, what is actually being measured is the level of various lipoproteins (like LDL and HDL).

Which brings us back to the subject at hand. The consensus belief, as I’m sure you’re aware, is that LDL is “bad” cholesterol and HDL is “good” cholesterol. High levels of LDL put us at risk for heart disease, and low levels of LDL protect us from it. Likewise, low levels of HDL are a risk factor for heart disease, and high levels are protective.

It such a simple explanation, and it helps drug companies to sell more than $14 billion dollars worth of “bad” cholesterol-lowering medications to more than 24 million American each year.

The only problem (for people who actually take the drugs, rather than sell them, that is) is the idea that all LDL cholesterol is “bad” is simply not true.

In order for cholesterol-carrying lipoproteins to cause disease, they have to damage the wall of an artery. The smaller an LDL particle is, the more likely it is to do this. In fact, a 1988 study showed that small, dense LDL are three times more likely to cause heart disease than normal LDL.

On the other hand, large LDL are buoyant and easily move through the circulatory system without damaging the arteries.

Think of it this way. Small, dense LDL are like BBs. Large, buoyant LDL are like beach balls. If you throw a beach ball at a window, nothing happens. But if you shoot that window with a BB gun, it breaks.

Another problem with small LDL is that they are more susceptible to oxidation. Oxidized LDL, or oxLDL, is formed when the fats in LDL particles react with oxidation and break down.

Researchers have shown that the smaller and denser LDL gets, the more quickly it oxidizes when they subject it to oxidants in a test tube.

Why does this matter? oxLDL is a far greater risk factor for heart disease than normal LDL. A large prospective study by Meisinger et al. showed that participants with high oxLDL had more than four times the risk of a heart attack than patients with lower oxLDL.

I hope it’s clear by now that the notion of “good” and “bad” cholesterol is misleading and incomplete. Not all LDL cholesterol is the same. Large, buoyant LDL are benign or protect against heart disease, whereas small, dense LDL are a significant risk factor. If there is truly a “bad” cholesterol, it is small LDL. But calling all LDL “bad” is a dangerous mistake.

Low-fat, high-carb diets raise “bad” cholesterol and lower “good” cholesterol

Here’s where the story gets even more interesting. And tragic.

Researchers working in this area have defined what they call Pattern A and Pattern B. Pattern A is when small, dense LDL is low, large, buoyant LDL is high, and HDL is high. Pattern B is when small, dense LDL is high, HDL is low, and triglycerides are high. Pattern B is strongly associated with increased risk of heart disease, whereas Pattern A is not.

It is not saturated fat or cholesterol that increases the amount of small, dense LDL we have in our blood. It’s carbohydrate.

Dr. Ronald Krauss has shown that reducing saturated fat and increasing carbohydrate intake shifts Pattern A to Pattern B – and in the process significantly increases your risk of heart disease. Ironically, this is exactly what the American Heart Association and other similar organizations have been recommending for decades.

In Dr. Krauss’s study, participants who ate the most saturated fat had the largest LDL, and vice versa.

Krauss also tested the effect of his dietary intervention on HDL (so-called “good” cholesterol). Studies have found that the largest HDL particles, HDL2b, provide the greatest protective effect against heart disease.

Guess what? Compared to diets high in both total and saturated fat, low-fat, high-carbohydrate diets decreased HDL2b levels. In yet another blow to the American Heart Association’s recommendations, Berglund et al. showed that using their suggested low-fat diet reduced HDL2b in men and women of diverse racial backgrounds.

Here’s what the authors said about their results:

The results indicate that dietary changes suggested to be prudent for a large segment of the population will primarily affect [i.e., reduce] the concentrations of the most prominent antiatherogenic [anti-heart attack] HDL subpopulation.

Translation: following the advice of the American Heart Association is hazardous to your health.

Eating cholesterol reduces small LDL

The amount of cholesterol in the diet is only weakly correlated with blood cholesterol levels. A recent review of the scientific literature published in Current Opinion in Clinical Nutrition and Metabolic Care clearly indicates that egg consumption has no discernible impact on blood cholesterol levels in 70% of the population. In the other 30% of the population (termed “hyperresponders”), eggs do increase both circulating LDL and HDL cholesterol.

Why is this? Cholesterol is such an important substance that its production is tightly regulated by the body. When you eat more, the body produces less, and vice versa. This is why the amount of cholesterol you eat has little – if any – impact on the cholesterol levels in your blood.

Eating cholesterol is not only harmless, it’s beneficial. In fact, one of the best ways to lower small, dense LDL is to eat eggs every day! Yes, you read that correctly. University of Connecticut researchers recently found that people who ate three whole eggs a day for 12 weeks dropped their small-LDL levels by an average of 18 percent.

If you’re confused right now I certainly don’t blame you.

Let’s review what we’ve been told for more than 50 years:

  1. Eating saturated fat and cholesterol in the diet raises “bad” cholesterol in the blood and increases the risk of heart disease.
  2. Reducing intake or saturated fat and cholesterol protects us against heart disease.

Now, let’s examine what credible scientific research published in major peer-reviewed journals in the last decade tells us:

  1. Eating saturated fat and cholesterol reduces the type of cholesterol associated with heart disease.
  2. Replacing saturated fat and cholesterol with carbohydrates lowers “good” (HDL) cholesterol, raises triglyceride levels, and increases our risk of heart disease.

Dr. Krauss, the author of one of the studies I mentioned above, recently said in an interview published in Men’s Health, “Everybody I know in the field — everybody — recognized that a simple low-fat message was a mistake.”

In other words, the advice we’ve been given by medical “authorities” over the past half century on how to prevent heart disease is actually causing it.

I don’t know about you, but that makes me very angry. Heart disease is the #1 cause of death in the US. Almost 4 in 10 people who die each year die of heart disease. It directly affects over 80 million Americans each year, and indirectly affects millions more.

We spend almost half a trillion dollars treating heart disease each year. To put this in perspective, the United Nations has estimated that ending world hunger would cost just $195 billion.

Yet in spite of all this money spent, the best medical authorities can do is tell us the exact opposite of what we should be doing? And they continue to give us the wrong information even though researchers have known that it’s wrong for at least the past fifteen years?

Really?

Sometimes it seems like everything is backwards.

How to reduce small LDL

Eating fewer carbs is perhaps the best place to start. Reducing carbs has several cardio-protective effects. It reduces levels of small, dense LDL, reduces triglycerides, and increases HDL levels. A triple whammy.

Exercise and losing weight also reduce small, dense LDL. In fact, weight loss has been shown to reverse the evil Pattern B all by itself.

As we saw above, eating three eggs a day can reduce our small LDL by almost 20%. Interestingly, alcohol has also been shown to reduce small LDL by 20%.

In other words, if you want to reduce your risk of heart disease, do the opposite of the American Heart Association (and probably your doctor) tells you to do. Eat butter. Eat eggs. Eat traditional animal fats. Reduce your intake of carbs, vegetable oils and processed foods, and stay active and within a healthy weight range.

Testing your small LDL level

I’m not a fan of arbitrary testing. Our medical system is obsessed with testing. But where has testing has brought us with cholesterol and heart disease? Has it improved outcomes? On the contrary, we test for a number (total LDL) that tells us very little, and then medicate it downwards recklessly and expensively.

If you’re worried about your small LDL level, my advice would be to eat fewer carbohydrates, eat plenty of saturated fat and cholesterol (instead of vegetable oils), exercise, lose weight if you need to, and have a drink every now and then! Since this is the same advice I’d give you if you took a test that actually showed high levels of small LDL, I don’t see much value in doing the test.

However, if you need to see the test results to get motivated to make the changes I suggested above, by all means do the test. There are a few ways to go about it.

First, keep in mind that a regular cholesterol test at your doctor won’t tell you anything about your small LDL level. The standard tests measure your total cholesterol, LDL and HDL. But they don’t distinguish between the dangerous small LDL and benign or protective large LDL.

The fastest and cheapest, albeit most indirect, route is to test your blood sugar both before and then 60 minutes after a meal (this is called a “post-prandial” glucose test). The reason a post-prandial blood glucose test can be a rough indicator for small LDL is the same foods that trigger a rise in blood sugar also increase small LDL. Namely, carbohydrates.

Blood glucose monitors are readily available at places like Walgreens and cost about $10. You’ll also need lancets and test strips, which aren’t expensive either. If your post-prandial glucose is higher than 120 mg/dl, that may be suggestive of a higher than desired small LDL level. This test is not a perfect approximation of small LDL, but it’s the cheapest and and easiest way to get a sense of it.

If you want to get more specific, there are two tests I recommend for small LDL that use slightly different methodology:

  1. LDL-S3 GGE Test. Proteins from your blood are spread across a gel palette. As the molecules move from one end to the other, the gel becomes progressively denser. Large particles of LDL cholesterol can’t travel as far as the small, dense particles can, Dr. Ziajka says. After staining the gel, scientists determine the average size of your LDL cholesterol particles. Berkeley Heart Lab. About $15 with insurance.
  2. The VAP Test. Your sample is mixed into a solution designed to separate lipoproteins by density. Small, dense particles sink, and large, fluffy particles stay at the top. The liquid is stained and then analyzed to reveal 21 different lipoprotein subfractions, including dominant LDL size. The Vap Test. Direct cost is $40.






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THE SATURDAY ESSAY

The Questionable Link Between Saturated Fat and Heart Disease

Are butter, cheese and steak really bad for you? The dubious science behind the anti-fat crusade


Updated May 6, 2014 10:25 a.m. ET

RF Pictures/Corbis

"Saturated fat does not cause heart disease"—or so concluded a big study published in March in the journal Annals of Internal Medicine. How could this be? The very cornerstone of dietary advice for generations has been that the saturated fats in butter, cheese and red meat should be avoided because they clog our arteries. For many diet-conscious Americans, it is simply second nature to opt for chicken over sirloin, canola oil over butter.

The new study's conclusion shouldn't surprise anyone familiar with modern nutritional science, however. The fact is, there has never been solid evidence for the idea that these fats cause disease. We only believe this to be the case because nutrition policy has been derailed over the past half-century by a mixture of personal ambition, bad science, politics and bias.

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Our distrust of saturated fat can be traced back to the 1950s, to a man named Ancel Benjamin Keys, a scientist at the University of Minnesota. Dr. Keys was formidably persuasive and, through sheer force of will, rose to the top of the nutrition world—even gracing the cover of Time magazine—for relentlessly championing the idea that saturated fats raise cholesterol and, as a result, cause heart attacks.

This idea fell on receptive ears because, at the time, Americans faced a fast-growing epidemic. Heart disease, a rarity only three decades earlier, had quickly become the nation's No. 1 killer. Even President Dwight D. Eisenhower suffered a heart attack in 1955. Researchers were desperate for answers.

As the director of the largest nutrition study to date, Dr. Keys was in an excellent position to promote his idea. The "Seven Countries" study that he conducted on nearly 13,000 men in the U.S., Japan and Europe ostensibly demonstrated that heart disease wasn't the inevitable result of aging but could be linked to poor nutrition.

Critics have pointed out that Dr. Keys violated several basic scientific norms in his study. For one, he didn't choose countries randomly but instead selected only those likely to prove his beliefs, including Yugoslavia, Finland and Italy. Excluded were France, land of the famously healthy omelet eater, as well as other countries where people consumed a lot of fat yet didn't suffer from high rates of heart disease, such as Switzerland, Sweden and West Germany. The study's star subjects—upon whom much of our current understanding of the Mediterranean diet is based—were peasants from Crete, islanders who tilled their fields well into old age and who appeared to eat very little meat or cheese.

As it turns out, Dr. Keys visited Crete during an unrepresentative period of extreme hardship after World War II. Furthermore, he made the mistake of measuring the islanders' diet partly during Lent, when they were forgoing meat and cheese. Dr. Keys therefore undercounted their consumption of saturated fat. Also, due to problems with the surveys, he ended up relying on data from just a few dozen men—far from the representative sample of 655 that he had initially selected. These flaws weren't revealed until much later, in a 2002 paper by scientists investigating the work on Crete—but by then, the misimpression left by his erroneous data had become international dogma.

In 1961, Dr. Keys sealed saturated fat's fate by landing a position on the nutrition committee of the American Heart Association, whose dietary guidelines are considered the gold standard. Although the committee had originally been skeptical of his hypothesis, it issued, in that year, the country's first-ever guidelines targeting saturated fats. The U.S. Department of Agriculture followed in 1980.

Other studies ensued. A half-dozen large, important trials pitted a diet high in vegetable oil—usually corn or soybean, but not olive oil—against one with more animal fats. But these trials, mainly from the 1970s, also had serious methodological problems. Some didn't control for smoking, for instance, or allowed men to wander in and out of the research group over the course of the experiment. The results were unreliable at best.

But there was no turning back: Too much institutional energy and research money had already been spent trying to prove Dr. Keys's hypothesis. A bias in its favor had grown so strong that the idea just started to seem like common sense. As Harvard nutrition professor Mark Hegsted said in 1977, after successfully persuading the U.S. Senate to recommend Dr. Keys's diet for the entire nation, the question wasn't whether Americans should change their diets, but why not? Important benefits could be expected, he argued. And the risks? "None can be identified," he said.

In fact, even back then, other scientists were warning about the diet's potential unintended consequences. Today, we are dealing with the reality that these have come to pass.

One consequence is that in cutting back on fats, we are now eating a lot more carbohydrates—at least 25% more since the early 1970s. Consumption of saturated fat, meanwhile, has dropped by 11%, according to the best available government data. Translation: Instead of meat, eggs and cheese, we're eating more pasta, grains, fruit and starchy vegetables such as potatoes. Even seemingly healthy low-fat foods, such as yogurt, are stealth carb-delivery systems, since removing the fat often requires the addition of fillers to make up for lost texture—and these are usually carbohydrate-based.

The problem is that carbohydrates break down into glucose, which causes the body to release insulin—a hormone that is fantastically efficient at storing fat. Meanwhile, fructose, the main sugar in fruit, causes the liver to generate triglycerides and other lipids in the blood that are altogether bad news. Excessive carbohydrates lead not only to obesity but also, over time, to Type 2 diabetes and, very likely, heart disease.

The real surprise is that, according to the best science to date, people put themselves at higher risk for these conditions no matter what kind of carbohydrates they eat. Yes, even unrefined carbs. Too much whole-grain oatmeal for breakfast and whole-grain pasta for dinner, with fruit snacks in between, add up to a less healthy diet than one of eggs and bacon, followed by fish. The reality is that fat doesn't make you fat or diabetic. Scientific investigations going back to the 1950s suggest that actually, carbs do.

The second big unintended consequence of our shift away from animal fats is that we're now consuming more vegetable oils. Butter and lard had long been staples of the American pantry until Crisco, introduced in 1911, became the first vegetable-based fat to win wide acceptance in U.S. kitchens. Then came margarines made from vegetable oil and then just plain vegetable oil in bottles.

All of these got a boost from the American Heart Association—which Procter & Gamble, the maker of Crisco oil, coincidentally helped launch as a national organization. In 1948, P&G made the AHA the beneficiary of the popular "Walking Man" radio contest, which the company sponsored. The show raised $1.7 million for the group and transformed it (according to the AHA's official history) from a small, underfunded professional society into the powerhouse that it remains today.

After the AHA advised the public to eat less saturated fat and switch to vegetable oils for a "healthy heart" in 1961, Americans changed their diets. Now these oils represent 7% to 8% of all calories in our diet, up from nearly zero in 1900, the biggest increase in consumption of any type of food over the past century.

This shift seemed like a good idea at the time, but it brought many potential health problems in its wake. In those early clinical trials, people on diets high in vegetable oil were found to suffer higher rates not only of cancer but also of gallstones. And, strikingly, they were more likely to die from violent accidents and suicides. Alarmed by these findings, the National Institutes of Health convened researchers several times in the early 1980s to try to explain these "side effects," but they couldn't. (Experts now speculate that certain psychological problems might be related to changes in brain chemistry caused by diet, such as fatty-acid imbalances or the depletion of cholesterol.)

We've also known since the 1940s that when heated, vegetable oils create oxidation products that, in experiments on animals, lead to cirrhosis of the liver and early death. For these reasons, some midcentury chemists warned against the consumption of these oils, but their concerns were allayed by a chemical fix: Oils could be rendered more stable through a process called hydrogenation, which used a catalyst to turn them from oils into solids.

From the 1950s on, these hardened oils became the backbone of the entire food industry, used in cakes, cookies, chips, breads, frostings, fillings, and frozen and fried food. Unfortunately, hydrogenation also produced trans fats, which since the 1970s have been suspected of interfering with basic cellular functioning and were recently condemned by the Food and Drug Administration for their ability to raise our levels of "bad" LDL cholesterol.

Yet paradoxically, the drive to get rid of trans fats has led some restaurants and food manufacturers to return to using regular liquid oils—with the same long-standing oxidation problems. These dangers are especially acute in restaurant fryers, where the oils are heated to high temperatures over long periods.

The past decade of research on these oxidation products has produced a sizable body of evidence showing their dramatic inflammatory and oxidative effects, which implicates them in heart disease and other illnesses such as Alzheimer's. Other newly discovered potential toxins in vegetable oils, called monochloropropane diols and glycidol esters, are now causing concern among health authorities in Europe.

In short, the track record of vegetable oils is highly worrisome—and not remotely what Americans bargained for when they gave up butter and lard.

Cutting back on saturated fat has had especially harmful consequences for women, who, due to hormonal differences, contract heart disease later in life and in a way that is distinct from men. If anything, high total cholesterol levels in women over 50 were found early on to be associated with longer life. This counterintuitive result was first discovered by the famous Framingham study on heart-disease risk factors in 1971 and has since been confirmed by other research.

Since women under 50 rarely get heart disease, the implication is that women of all ages have been worrying about their cholesterol levels needlessly. Yet the Framingham study's findings on women were omitted from the study's conclusions. And less than a decade later, government health officials pushed their advice about fat and cholesterol on all Americans over age 2—based exclusively on data from middle-aged men.

Sticking to these guidelines has meant ignoring growing evidence that women on diets low in saturated fat actually increase their risk of having a heart attack. The "good" HDL cholesterol drops precipitously for women on this diet (it drops for men too, but less so). The sad irony is that women have been especially rigorous about ramping up on their fruits, vegetables and grains, but they now suffer from higher obesity rates than men, and their death rates from heart disease have reached parity.

Seeing the U.S. population grow sicker and fatter while adhering to official dietary guidelines has put nutrition authorities in an awkward position. Recently, the response of many researchers has been to blame "Big Food" for bombarding Americans with sugar-laden products. No doubt these are bad for us, but it is also fair to say that the food industry has simply been responding to the dietary guidelines issued by the AHA and USDA, which have encouraged high-carbohydrate diets and until quite recently said next to nothing about the need to limit sugar.

Indeed, up until 1999, the AHA was still advising Americans to reach for "soft drinks," and in 2001, the group was still recommending snacks of "gum-drops" and "hard candies made primarily with sugar" to avoid fatty foods.

Our half-century effort to cut back on the consumption of meat, eggs and whole-fat dairy has a tragic quality. More than a billion dollars have been spent trying to prove Ancel Keys's hypothesis, but evidence of its benefits has never been produced. It is time to put the saturated-fat hypothesis to bed and to move on to test other possible culprits for our nation's health woes.

Ms. Teicholz has been researching dietary fat and disease for nearly a decade. Her book, "The Big Fat Surprise: Why Butter, Meat and Cheese Belong in a Healthy Diet," will be published by Simon & Schuster on May 13.



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High Cholesterol And Heart Disease — Myth or Truth?

The Response-to-Injury Rabbit Never Developed Atherosclerosis — Why Not?

August 23, 2008

by Chris Masterjohn

The pop science version of cholesterol goes something like this: when you eat fatty foods, especially foods rich in animal fat, the saturated fat and cholesterol in these foods wind up in your blood and stick to your arteries. Since saturated fats are solid outside your body, they will be solid inside your body too — depsite the 30-degree increase in average temperature. Arteries are much like pipes. When they get caked up with grease, blood flow is impaired, and a heart attack ensues.

None of the prominent scientists who promoted the idea that cholesterol is a critical factor in the development of heart disease ever believed anything remotely resembling this nonsense. From the beginning, they recognized that atherosclerotic plaque accumulates behind the layer of the artery in contact with the blood, called the endothelium, and that the cholesterol and fat within it is engulfed in white blood cells.

The theory these scientists promoted looked something like this: when the cholesterol level in the blood increases, it penetrates the arterial wall and gets stuck; white blood cells circulating in the blood then enter the arterial wall and gobble up the cholesterol; the accumulation of lipid-loaded white blood cells causes local injury, leading to cell death, calcification, and the development of a collagen-laden "fibrous cap" over the atherosclerotic lesion. When the cap ruptures, the blood clots, blocking the artery and causing a heart attack. This is called the lipid hypothesis.

But is this true? Books and web sites devoted to debunking this theory have come out of the woodwork over the last decade; books defending it have followed suit. Consider the following titles to see just how controversial the idea really is:

So is the theory that cholesterol causes heart disease just a myth? Or are the skeptics truly waging a war against the preponderance of the evidence?

In this Article:

The Cholesterol Debate — What Causes Atherosclerosis?

The truth is that each of these authors makes important points. Were there never any good evidence that cholesterol was involved in heart disease, there would be no National Cholesterol Education Program, no statin empire, and Daniel Steinberg could never have written a book plus over 200 scientific papers on the subject. On the other hand, were there never anything seriously wrong with the mainstream dogma on the issue, Ravnskov, Colpo, Kendrick, and many other authors could never have built their careers around pointing out the gaping holes in the theory.

There is no one cause of "heart disease." "Heart disease" is a heterogeneous compliation of diseases of the heart and blood vessels with many different causes. Some of these include disturbances of the rhythm of the heart, calcification of the middle portion of the blood vessels and calcification of the heart valves, and congestive heart failure. The question I address in this article is whether and in what sense cholesterol is involved in atherosclerosis, the development of fatty and calcified plaques in isolated, raised lesions, which can cause heart attacks by rupturing, clotting, and blocking arteries.

In 1933, the famous proponent of the cholesterol-fed rabbit model Nikolai Anitschkov declared that atherosclerosis had been shown to be of an "infiltrative" character rather than a "degenerative" character and was driven by lipids (fatty substances) rather than by inflammation. He did not deny inflammation was involved, but believed that it was secondary to lipid infiltration. Many opponents continue to claim that the root cause driving heart disease has nothing to do with lipids and everything to do with inflammation and that it is degenerative rather than infiltrative in character.

As we will see below, these are all correct! Atherosclerosis is largely driven by the degeneration of lipids which infiltrate the blood vessel and thereby cause inflammation. Inflammation from other sources may accelerate the process or further the degeneration of the atherosclerotic plaques once they are formed, but the initiating factor for fatty plaques appears to be the degeneration of lipids — especially the degeneration of polyunsaturated fatty acids (PUFA).

In order to begin looking at the evidence, we must go back a century in time to the cholesterol-fed rabbit. The cholesterol-fed rabbit model came on the heels of extensive investigations into what would later be termed the "response-to-injury hypothesis."

The Response-to-Injury Rabbit Model

Around the turn of the twentieth century, research into the cause or causes of heart disease was in full throttle. A 1933 compilation edited by E.V. Cowdry entitled Arteriosclerosis: A Survey of the Problem (New York: Macmillan) contained twenty reviews of investigations into the matter, including statistical relationships, the distribution of the disease in wild animals, the distribution in humans according to race and climate, nutritional influences, the physical and chemical nature of the changes that occur in atherosclerotic tissues, and experimental models of the disease.

Nikolai Anitschkov, who developed the cholesterol-fed rabbit model, wrote the 50-page review of experimental animal models.1 Much of this research was published in German, so Anitschkov's review is an invaluable resource.

According to Anitschkov, early ideas about the origin of arteriosclerosis — a general term for hardening and damage to the arteries, of which atherosclerosis is a specific type — saw the diseases as a response to injury. The injury was primarily seen as either a mechanical or a toxic factor, and was sometimes believed to be injury to the nerves rather than injury to the blood vessels. Researchers carried out a multitude of experiments on rabbits and other animals, including the following:

  • Mechanical damage to the blood vessels including ligating, pulling, pinching, and wounding them, and cauterizing them with galvanic wire or silver nitrate.
  • Increasing blood pressure by constricting the blood supply through the aorta, damaging the kidneys, or hanging rabbits up by their feet.
  • Severing or irritating certain nerves.
  • Injecting rabbits with adrenalin.
  • Injecting rabbits with a multitude of toxic factors, including digitalin, strophanthin, adonidin, ergotin, theocin, barium chloride, hydrastin, nicotine, caffeine, formalin, ergosterol, and various salts of acids and heavy metals.
  • Injection of diphtheria toxin and many other bacteria cultures or bacterial byproducts.

Most of these methods caused substantial damage to the arteries and resulted in a "regenerative thickening" of one or another type. So the response-to-injury concept is quite real.

Atherosclerosis is Just One Type of Arteriosclerosis

None of these methods, however, produced anything resembling human atherosclerosis. While arteriosclerosis refers to hardening and degeneration of the arteries in general, atherosclerosis is a specific type of arteriosclerosis in which a plaque rich in lipid-loaded white blood cells, cholesterol, fatty acids, calcium, various debris — called an atheroma — invades the innermost layer of the blood vessel wall called the intima, just behind the one-cell-thick layer called the endothelium. If you are not familiar with the anatomy of a blood vessel, you can see a diagram of it here.

The research in Anitschkov's day suggested that, while various types of arteriosclerosis occurred in humans, atherosclerosis was a much more important cause of death. Anitschkov thus concerned his research with what caused atherosclerosis.

The mechanical injuries to blood vessels or nerves produced a local repair process that involved the proliferation of cells, their congregation around the damaged area, and a resultant thickening of the vessel wall. The results were local rather than systemic, however, and never produced a lesion resembling an atheroma.

Injections of adrenalin produced much more interesting changes that were much more relevant to humans. They produced necrosis (death) of cells in the media followed by extensive calcification. A similar process was observed in some of the blood pressure experiments and in many of the experiments involving injections of metallic, bacterial, or other toxins. These changes, however, were fundamentally different from atherosclerosis, which occurs in the intima.

Medial Calcification and the Vitamin K2 Connection

That does not mean this research is irrelevant. Humans experience this type of medial calcification in diabetes, kidney disease, and aging. It appears to assault the media of arteries and the valves of the heart together. It increases arterial stiffness and decreases the artery's ability to accomodate moderately high levels of blood pressure. One of the most important factors in this type of calcification appears to be vitamin K2.

Vitamin K-dependent proteins protect against cell death, help clear away the debris that cells leave behind when they do die, and protect against the calcification of soft tissues. In the absence of sufficient vitamin K, these proteins are deformed and fail to work properly. It appears that vitamin K2, found in animal fats and fermented foods, is far more important in this respect than vitamin K1, found in green plant foods. I have written extensively on this subject and argued that vitamin K2 is the "activator X" of Weston Price in my article, On the Trail of the Elusive X Factor: Vitamin K2 Revealed.

Despite the research in Anitschkov's day suggesting that only atherosclerosis had major clinical importance, research in our own day shows that calcification of the media and valves is critically important to, at a minimum, the 324 million people worldwide who will be diabetic come 2025. For the US population born in 2000, the estimated lifetime risk of type 2 diabetes is one in three.2 In type 2 diabetics, medial calcification increases the risk of mortality from heart disease, stroke, and all causes. It also predicts the incidence of heart disease and stroke, including events that do not produce fatalities, and predicts the likelihood that peripheral artery disease will require limb amputation.3

So the response-to-injury hypothesis has a solid basis of evidence for arteriosclerosis of the media, and this is clinically important — but what causes atheroma, that is, the fatty plaque that causes raised lesions in the intima of the blood vessels?

To answer this question, we must look to the cholesterol-fed rabbit.

The Cholesterol-Fed Rabbit Controversy

In 1909, a researcher at the Military Medical Academy in St. Petersburg named Ignatowski produced atherosclerosis in rabbits by feeding them a diet of meat, eggs, and milk. He was pursuing a hypothesis put forward by Nobel Prize-winning microbiologist I. Metchnikov that dietary protein accelerated aging.4

In 1913, Anitschkov and his partner Chalatov were studying at the same academy and were assigned to follow up Ignatowski's work. They progressively narrowed down the causative factor to cholesterol by feeding different foods and fractions of foods, finally producing the diease by feeding pure cholesterol dissolved in sunflower oil.4

Rabbits fed sunflower oil alone did not develop atherosclerosis. In the cholesterol-fed rabbits, however, lesions developed that exhibited a remarkable similarity to the human disease. They began as fatty streaks in the intima; circulating white blood cells then invaded the intima and engulfed the cholesterol and fat deposited there, eventually growing into large phagocytic cells that Anitschkov called xanthoma cells and we now call foam cells; eventually the developing plaque protruded into the intima in the form of a raised lesion. The lesion possessed a fatty core rich in crystalized and calcified cholesterol deposits and was covered with a fibrous cap.1

The lesions did not appear everywhere equally, but occurred in specific areas. They were most prominent in the aorta and other large arteries, especially in the areas of the artery wall that experience disturbed blood flow such as the points where the arteries branch. While they did not occur in exactly the same places as human atherosclerotic lesions, the pattern was largely similar and the underlying physiological principle dictating the location of the lesions — mainly the type of blood flow experienced by the artery wall — was the same.1

The rabbits developed cholesterol deposits all throughout their bodies, in their eyes and internal organs. Anitschkov produced a more mild form of the disease, however, by feeding the rabbits milk. In these experiments, the rabbits received a much more moderate amount of cholesterol over a much longer period of time and the resulting disease was much more focused in the arteries.1

One curious difference between rabbits and humans is that when rabbits develop atherosclerosis, their plaques never rupture and they never get heart attacks. The main determinant of plaque rupture according to the current scientific literature is the balance between collagen degradation and collagen synthesis.5 Collagen synthesis requires vitamin C. Most animals, including rabbits, make their own vitamin C, but humans do not.

Atherosclerosis itself probably diminishes the quality of life in many different ways by impeding blood flow and blood vessel function, but it clearly does not inexorably lead to heart attacks. The reason why atherosclerosis produces heart attacks in humans and not rabbits or many other animals might be that humans cannot produce their own vitamin C.

Cholesterol in the Blood, Not the Food

Anitschkov argued against calling cholesterol "the cause" of atherosclerosis, but he considered cholesterol the primary causal factor and the necessary causal factor. Mechanical injuries, adrenalin injections, and other methods used to induce various types of arteriosclerosis would accelerate the development of atheroma when they were combined with cholesterol-feeding, but they would never result in human-like atherosclerosis by themselves.

Anitschkov never concluded from his experiments that cholesterol in the diet caused atherosclerosis in humans, however. To the contrary, he wrote the following:

[I]n human atherosclerosis the conditions are different. It is quite certain that such large quantities of cholesterin are not ingested with the ordinary food. In human patients we have probably to deal with a primary disturbance of the cholesterin metabolism, which may lead to atherosclerosis even if the hypercholesterinemia is less pronounced, provided only that it is of long duration and associated with other injurious factors.

Cholesterol skeptics often argue that the rabbit is irrelevant to the human because it is an herbivore. Cholesterol-feeding has failed to produce atherosclerosis in many other species. This is true, but it misses the point. In the species where cholesterol-feeding alone does not produce atherosclerosis, the blood level of cholesterol does not rise as much as in rabbits. But in all of these species when the level of cholesterol in the blood rises high enough, atherosclerosis ensues. For example, feeding dogs cholesterol alone does not produce atherosclerosis because they turn the cholesterol into bile acids; but inhibiting thyroid hormone stops them from making this conversion, and when combined with cholesterol-feeding, it induces atherosclerosis.

As Steinberg points out, raising blood levels of cholesterol has produced atherosclerosis in baboons, cats, chickens, chimpanzees, dogs, goats, guinea pigs, hamsters, monkeys, mice, parrots, pigs, pigeons, rabbits and rats.

The role of blood cholesterol in human heart disease was supported by research showing that people with a disorder that would eventually be called familial hypercholesterolemia had dramatically increased blood levels of cholesterol and, in youth and middle age, dramatically increased relative risks of heart disease and atherosclerosis. But what caused their high cholesterol levels, and did those levels cause the atherosclerosis, and if so, did this phenomenon have any relevance to the rest of us?

And, if cholesterol was somehow the culprit in all of this, was it merely its concentration in the blood that was at play, or was something very different going on?

Lessons From Familial Hypercholesterolemia

Familial hypercholesterolemia (FH) bears a striking resemblance to the cholesterol-fed rabbit model. In mild cases, it produces earlier and more rapidly developing atherosclerosis compared to the general population. In its severe cases, it results in cholesterol deposits all throughout the body, especially in the liver, kidneys, and eyelids.4

In the mid-1970s, Brown and Goldstein discovered that FH resulted from a single genetic defect in the LDL receptor that made the cells unable to absorb LDL from the bloodstream. Steinberg argues that, since cells jealously guard their cholesterol concentrations by adjusting their synthesis of cholesterol as needed, this showed that FH patients differed from the general population in only one single way: the concentration of cholesterol in their blood.4

The finding drew several more parallels between FH and Anitschkov's cholesterol-fed rabbits. Anitschkov argued that it was not the mere feeding of cholesterol to the rabbits that produced atherosclerosis, but the overwhelming of their capacity to use and dispose of that cholesterol. FH cells could absorb free cholesterol, but not cholesterol from LDL. Anitschkov's rabbits developed atherosclerosis when they ate cholesterol, but not when they were injected with it — in which case it would not be packaged into lipoproteins such as LDL, which contain many other substances besides cholesterol. Looking backward, it appears that the common thread running through each model was that the level of LDL in the blood exceeded the capacity of the LDL receptors to move that LDL from the blood to the cells.

The LDL receptor highway was blocked, and the LDL traffic was jammed.

Is Steinberg correct, however, that this changes nothing but the concentration of LDL in the blood? Consider what happens in a traffic jam:

  • The concentration of cars in the road increases.
  • It takes you longer to get home.

When LDL can't get from the blood into the cells, its concentration in the blood rises, but it also spends a longer amount of time in the blood. Why would that matter? This would become clear just several years later. At the end of the 1970s, the role of oxidative stress in heart disease would finally become clear.

The Role of Oxidized LDL in Heart Disease

Anitschkov believed that his research showed that atherosclerosis was of an infiltrative character rather than a degenerative character. He believed that cholesterol and other substances naturally permeated the endothelium in order to nourish the other layers of the blood vessels, and proceeded from there into the lymph fluid. When the blood level of cholesterol rose sufficiently, he argued, it entered the intima at a faster rate than it could exit and began to accumulate.

Anitschkov was correct that the disease was driven by an infiltration of lipid, and he was correct that the degeneration of the blood vessel wall was secondary to this infiltration. What he failed to realize, and could not have realized at the time, was that the entire process depended on the degeneration of the lipid.

The Discovery of Oxidized LDL

Beginning in 1979, investigators made a series of revolutionary discoveries revealing this degenerative process. When they incubated cells with LDL in the absence of other serum components, the cells underwent severe damage and began to die within 24 hours. Adding serum or HDL prevented the toxicity.4

In 1981, these researchers discovered that culturing endothelial cells with LDL caused dramatic changes to the LDL, making it denser, more electronegative, and giving it a dramatic ability to accumulate in white blood cells called macrophages. Macrophages are phagocytic, meaning they like to gobble up other things, and they are the precursors to the "foam cells" that populate atherosclerotic plaques. The researchers called this LDL "endothelial cell-modified LDL." Soon after, they discovered that the LDL was being "oxidatively modified" and that not only HDL but vitamin E (which HDL is rich in) prevented the effect.4

Oxidized LDL Causes Injury and Inflammation

Since those early findings, thousands of papers have now been published on the role of oxidized LDL in the development of atherosclerosis. Oxidized LDL causes endothelial cells to secrete "adhesion molecules" and "chemoattractants" that allow white blood cells called monocytes to penetrate in between the endothelial cells and stick to them in the subendothelial space where fatty streaks and atherosclerotic plaques develop.6

Oxidized LDL turns on the expression of genes in monocytes which cause them to convert into macrophages and eventually into foam cells, which makes them gobble up more and more oxidized LDL endlessly — but these macrophages use "scavenger receptors" rather than LDL receptors, so they never take up meaningful amounts of non-oxidized LDL; they only take up oxidized LDL, and it is oxidized LDL itself that initates this endless cycle.7

Oxidized LDL initiates the inflammatory process by causing foam cells to secrete molecules that attract T cells and other inflammatory cells.6 Oxidized LDL enhances the process whereby T cells, foam cells, smooth muscle cells and endothelial cells decrease collagen production and increase collagen degradation, which leads to the rupture of the fibrous plaque.5

Endothelial cells produce nitric oxide, a gas that protects LDL from oxidation, increases blood flow, decreases the adhesion of monocytes to the endothelium, and decreases blood clotting. Oxidized LDL impairs the endothelial cell's ability to produce nitric oxide.8

In short, oxidized LDL contributes to the entire atherosclerotic process from start to finish. Writers who argue that atherosclerosis has nothing to do with lipids but is all about inflammation and response to injury must contend with the fact that oxidized LDL injures endothelial cells and causes inflammation!

Small, Dense (Pattern B) LDL and Oxidation — Which Comes First?

If it is oxidized LDL rather than LDL per se that contributes to atherosclerosis, the question arises of what causes LDL to oxidize. Since polyunsaturated fatty acids (PUFA) in the LDL membrane are the components that are most vulnerable to oxidation, excess PUFA and insufficient antioxidants would seem to be the most obvious culprits. Endothelial cells, however, secrete a number of oxidative enzymes such as myeloperoxidase and lipoxygenase. LDL is always exposed to endothelial cells in the blood, but if it makes its way into the subendothleial space where it can get stuck in a network of sugary proteins called proteoglycans, it would be exposed to them even more directly. Some researchers have therefore put forward the "response-to-retention hypothesis," wherein the LDL oxidizes in response to getting stuck in the subendothelial space.

In 1988, a case-control study showed that people with a preponderance of small, dense LDL were three times more likely to suffer from a heart attack.9 Researchers subsequently showed that the smaller and denser LDL gets, the more quickly it oxidizes when they subject it to oxidants in a test tube.10 Then the "response-to-retention" crowd jumped in on the game a few years later and showed that small, dense LDL were much more likely get stuck in test tube versions of the proteoglycan network of the subendothelial space.11

If the response-to-retention hypothesis is true, we are back to the infiltration hypothesis where the accumulation of LDL in the subendothelial space is driving the whole process because the accumulation causes the oxidation. This would be a convenient way of circumventing the enormously embarassing fact that the medical establishment has been pushing highly oxidation-prone PUFA oils for fifty years.

The question is, how are these LDL getting small and dense?

Within the response-to-retention paper, the authors stated that "with decreasing size and increasing density the LDL particles have less of the non-polar core covered with a surface monolayer made of phospholipids and cholesterol."

Where did the phospholipid membrane go?

A group working on lipoprotein (a), or Lp(a), published a paper in July of this year showing that virtually all oxidized LDL in the blood circulates attached to Lp(a). Lp(a) is essentially LDL stuck to a protein called apolipoprotein (a) or apo(a). This group showed that when oxidized LDL and apo(a) are incubated together, many of the oxidized phospholipids transfer directly to the apo(a).12 In other words, when the membrane of LDL begins to oxidize, parts of it hop right off the LDL particle. Could that explain why "less of the non-polar core" would be "covered with a surface monolayer" on some LDL particles?

When Steinberg and his coworkers first described the characteristics of "endothelial cell-modified LDL," one of the most conspicuous changes that occurred to the LDL particles was a marked increase in density.13

A 1997 study confirmed that the LDL taken from people with a preponderance of the small, dense type does indeed oxidize quicker in a test tube, but the oxidation status of the LDL was different before they subjected it to oxidation. The predominantly small, dense LDL had a higher ratio of oxidized-to-reduced coenzyme Q10 and a lower CoQ10-to-vitamin E ratio.14 Since CoQ10 is the first line of defense against LDL oxidation, this study strongly suggested that oxidation of the small, dense LDL had already started.

So here we have a chicken-and-egg question. Does small, dense LDL oxidize more rapidly in a test tube because it is small and dense, or because it is already partially oxidized, and its antioxidant defenses are already partially depleted? Is small, dense LDL more vulnerable to oxidation, or does LDL become small and dense when it becomes oxidized?

If LDL becomes small and dense through oxidation, then even if the test tube studies on its "stickiness" are correct and small, dense LDL is more likely to get stuck in the sugary protein network behind the endothelium, it is the oxidation driving the stickiness and not the stickiness driving the oxidation.

So we are back to square one wondering why the medical establishment never announed an emergency measure to put all the research dollars into discovering just how much damage it had done to everyone who followed its recommendations to use high-PUFA vegetable oils in place of saturated animal fats over the last fifty years.

Oxidized LDL and the PUFA Connection

Let us return to the traffic analogy for a moment. Why would an "LDL traffic jam," wherein the "LDL receptor highway" is blocked contribute to atherosclerosis?

The membrane of LDL contains polyunsaturated fatty acids (PUFA), which are highly vulnerable to oxidation. Cells continuously make antioxidant enzymes and other antioxidant compounds to protect their membrane PUFA. If PUFA start to oxidize, the cell ramps up its antioxidant production. When the liver packs cholesterol into a VLDL particle and secretes it into the blood (where it eventually becomes an LDL particle after delivering some of its nutrients to other tissues), it puts some antioxidants into the package. The PUFA have now left the comparative safety of the liver cell and have only a limited supply of antioxidants. When those antioxidants are used up, the PUFA begin to oxidize, and their oxidation products proceed to damage other components of the lipoprotein. When the oxidation becomes severe, the oxidized LDL winds up in a foam cell in an atherosclerotic plaque.

Let's draw another analogy, this time to a jar of oil. If you use a jar of oil, you open it, exposing the PUFA within it to the oxygen in the air, but quickly put the cap back on and put it back in the fridge. What would happen if you opened the jar and let it sit on the table at room temperature? Over time, the limited amount of antioxidants in the oil would run out and the PUFA would begin to oxidize. The oil would go rancid.

Pumping LDL into the blood but letting it sit there circulating round and round exposed to oxidants rather than taking it into the shelter of the cell is like opening a jar of oil and leaving it on the table.

LDL taken from people who consume more PUFA, whether from vegetable oil or fish oil, oxidizes more easily in a test tube. Alpha-tocopherol, the major form of vitamin E, does not help.15

The specific components of the oxidized LDL particle that interact with the DNA of monocytes to transform them into macrophages and then into foam cells are oxidized derivatives of linoleic acid, a PUFA found in vegetable oils.16

A 2004 study from Brigham and Women's Hospital and Harvard School of Public Health showed that in postmenopausal women, the more PUFA they ate, and to a much lesser extent the more carbohydrate they ate, the worse their atherosclerosis became over time. The more saturated fat they ate, the less their atherosclerosis progressed; in the highest intake of saturated fat, the atherosclerosis reversed over time.17

I will cover the topic of saturated fat, PUFA, and heart disease in greater detail in another article on the diet-heart hypothesis. Additionally, I have written a Special Report entitled How Essential Are the Essential Fatty Acids? that provides accurate and thoroughly researched information on the true requirement for PUFA, which is negligible for healthy adults. As part of my Special Reports series, I will be publishing a second PUFA Report later this year that will cover the benefits and dangers of consuming PUFA in amounts larger than the minimum requirements.

Shear Stress Explains the Locations of Plaques and the Benefits of Exercise

As in the cholesterol-fed rabbit, human atherosclerosis occurs in discrete plaques at specific locations. In both species, these plaques occur in locations that experience disturbed blood flow, such as the points where the arteries branch.

Anitschkov showed that the endothelium was more permeable to molecules labeled with dye at these points. Experimental vessel injuries that caused inflammatory responses made the endothelium even more permeable, but even in the absence of any treatment, the endothelium was naturally permeable in these areas.1

Sections of the arterial wall in these areas experience a lower level of shear stress than sections in other areas. Shear stress is the type of pressure that is caused by laminar blood flow, or the flow of blood parallel to the blood vessel wall. Shear stress decreases the permeability of the endothelium by stimulating the production of the proteins that form the junctions between the endothelial cells. Under levels of shear stress approximating those that exist at locations where atherosclerosis develops, easily visualizable gold particles the size of LDL particles slip right in between the endothelial cells, whereas the permeability to these particles is very low under levels of shear stress approximating those that exist where plaques do not develop.18

Shear stress also increases nitric oxide production. Nitric oxide increases blood vessel dilation and blood flow, decreases the adhesion of monocytes to the endothelium, decreases blood clotting, and prevents the oxidation of LDL.6

By increasing blood flow, exercise increases shear stress. Since the average shear stress over time seems to be the critical factor, exercise might help prevent atherosclerosis by decreasing the permeability of the endothelium and increasing nitric oxide production in those areas of the blood vessels where the resting level of shear stress is insufficient for protection.

What About Correlations with High Cholesterol?

Much of the cholesterol debate focuses on correlations with cholesterol. How strong are they? How consistent are they? Why do they show up in young people but not in old, in men more than women?

The debate really misses the point, because since the early 1980s the molecular evidence has made very clear that it is oxidized LDL that contributes to atherosclerosis.

Correlations with cholesterol are likely to be confounded by a variety of factors that simultaneously increase cholesterol levels and contribute to heart disease, like stress and inflammation. In fact, inflammation seems to increase cholesterol synthesis essentially as an accidental byproduct of activating the stress response through an enzyme called Rho. Rho slashes nitric oxide production and thus almost certainly makes a contribution to atherosclerosis. For more information on Rho activation, click here.

Researchers have only recently developed methods for testing levels of oxidized LDL. One group has developed an antibody that recognizes oxidized but not non-oxidized phospholipids. They have shown that the proportion of LDL-associated phospholipids that are oxidized is a much more impressive risk factor for heart disease than LDL, and when it is multiplied by the level of LDL, thus indicating the total concentration of oxidized phospholipids, it is even better. Its predictive value is lower in older people, but still strong.19

Why would the association decline with age? If we look at the totality of the evidence about the mechanisms of atherosclerosis, it appears that oxidized LDL is the necessary initiating factor, but that we should expect its prominence as a contributing factor to decrease over time. Atherosclerosis probably does not develop in the absence of oxidized LDL. Once it does develop, however, and once the oxidized LDL stimulates the formation of foam cells, those foam cells recruit T cells that make their own contribution to the inflammatory process. Animal experiments show that independent sources of inflammation cannot initiate atherosclerosis, but they can aggravate it or accelerate it. Vitamin C deficiency, systemic infection, stress, and many other factors likely make contributions alongside oxidized LDL to the weakening and rupture of the fibrous cap that ultimately leads to a heart attack.

Virtually everyone develops substantial atherosclerosis by the time they are old. In people with more oxidized LDL, it occurs faster, and consequently reaches an advanced stage at a younger age. Inflammation will not help rupture a plaque that does not exist, so it will be much less likely to cause a heart attack in a younger person unless that person has high levels of oxidized LDL and consequently advanced atherosclerosis. In an older population wherein most people have advanced plaques, the factors that weaken the plaque will become much more important than the factors that create the plaque.

Studying the issue is complicated by the fact that we are looking at oxidized LDL in the blood. Once LDL gets oxidized enough, presumably it will wind up in arterial plaque. If there are factors that protect circulating LDL from contact with the tissues it could harm, they could confound the association.

Finally, studies looking at cardiovascular incidence or mortality are confounded by the fact that atherosclerosis is only one type of arteriosclerosis, and arteriosclerosis is only one cause of cardiovascular disease. Medial calcification, arrhythmia, congestive heart failure, or other causes of emboli (particles that can cause vessels) may all contribute to cardiovascular events. Oxidized LDL should only, or at least primarily, correlate with those events caused by atherosclerosis.

So is the Lipid Hypothesis Correct?

So is the lipid hypothesis correct? Not in its original form. The weight of the evidence clearly supports a role for the oxidation of LDL and not the concentration of LDL in the blood in the development of atherosclerosis.

The oxidized lipid hypothesis has an enormous amount of evidence supporting it. The cholesterol-fed rabbit model was a model not merely of hypercholesterolemia but of hyper-oxidized-lipoproteinemia. Antioxidants cause major decreases in atherosclerosis in cholesterol-fed or Watanabe familial hypercholesterolemic rabbit models independent of cholesterol levels.4,20

We should not expect antioxidants to be fully capable of preventing the oxidation of LDL by themselves. As I discuss in my PUFA Report, antioxidants can stop oxidized PUFA from damaging other PUFA, but they can never fully repair the oxidized PUFA. The best they can do is convert it to a hydroxy-fatty acid, and it is the hydroxy versions of linoleic acid that have been shown to convert monocytes to foam cells!

Thus, all three of the following critical factors must be addressed:

  • Increasing antioxidant status, especially coenzyme Q10, but also alpha- and gamma-tocopherol.
  • Reducing PUFA intake.
  • Increasing LDL receptor function to minimize the amount of time LDL spends in the bloodstream.

If concentrations of LDL rise in the blood because the LDL is not being utilized — for example, in familial hypercholesterolemia — then the LDL is exposing its vulnerable PUFA to conditions promoting oxidative stress for too long. The solution should not be to diminish cholesterol synthesis, imparing CoQ10 synthesis along with it, but to increase LDL utilization. The appropriate nutritional strategies for increasing LDL utilization desperately need to be researched.

A recent study showed that curcumin, a component of tumeric, increases the expression of the LDL receptor. This study may provide valuable clues. Thyroid hormone is important to the function of the LDL receptor, and many people likely have suboptimal thyroid status.

The irony in all of this is that there is no evidence to suggest that cholesterol is the culprit. In the rabbit, consuming large amounts of cholesterol increases the exposure of LDL membrane-associated PUFA to oxidation because it causes their translocation from the liver to the blood where they are detached from the cellular environment and less protected. In humans, eating cholesterol in the form of several eggs per day probably decreases the vulnerability of LDL to oxidation. See here.

The higher the concentration of free cholesterol within the LDL particle, the less vulnerable it is to oxidation. By contrast, the higher the concentration of cholesterol that is linked to fatty acids, called "esterified cholesterol," the more vulnerable the LDL is to oxidation.9 Esterified cholesterol primarily exists in the core of the particle. Free cholesterol primarily exists in the surface membrane where the initial oxidation takes place, so cholesterol seems to protect the PUFA from oxidation.

So, does cholesterol cause atherosclerosis? No!

But do blood lipids? Yes. Atherosclerosis is a disease in which degenerating lipids infiltrate the blood vessel wall and cause inflammation and degeneration of the local tissue once they arrive there. Solid evidence has amassed in favor of this view for the last 100 years.

You can peruse the references, share this article, or leave a comment below.

Read more about the author, Chris Masterjohn, PhD, here.

How Essential Are the Essential Fatty Acids?

The PUFA Report Part 1: A Critical Review of the Requirement for Polyunsaturated Fatty Acids

By Chris Masterjohn. Cholesterol-And-Health.Com Special Reports Volume 1 Issue 2. 25 pages, 3 figures, 114 references. $15.00

Abstract

Current reviews and textbooks call the omega-6 linoleic acid and the omega-3 alpha-linolenic acid "essential fatty acids" (EFA) and cite the EFA requirement as one to four percent of calories. Research suggests, however, that the omega-6 arachidonic acid (AA) and the omega-3 docosahexaenoic acid (DHA) are the only fatty acids that are truly essential. Eicosapentaenoic acid (EPA) occurs in fish products but is probably not a normal constituent of the mammalian body and in excess it interferes with essential AA metabolism. 

The EFA requirement cited in the scientific literature is inflated by several factors: the use of diets composed mostly of sucrose, glucose, or corn syrup; the use of diets deficient in vitamin B6; the use of purified fatty acids instead of whole foods; the use of questionable biochemical markers rather than verifiable symptoms as an index for EFA deficiency; and the generalization from studies using young, growing animals to adults.

The true requirement for EFA during growth and development is less than 0.5 percent of calories when supplied by most animal fats and less than 0.12 percent of calories when supplied by liver. 

On diets low in heated vegetable oils and sugar and rich in essential minerals, biotin, and vitamin B6, the requirement is likely to be much lower than this. 

Adults recovering from injury, suffering from degenerative diseases involving oxidative stress, or seeking to build muscle mass mass may have a similar requirement. 

For women who are seeking to conceive, pregnant, or lactating, the EFA requirement may be as high as one percent of calories. 

In other healthy adults, however, the requirement is infinitesimal if it exists at all. 

The best sources of EFAs are liver, butter, and egg yolks, especially from animals raised on pasture. During pregnancy, lactation, and childhood, small amounts of cod liver oil may be useful to provide extra DHA, but otherwise this supplement should be used only when needed to obtain fat-soluble vitamins. Vegetarians or others who eat a diet low in animal fat should consider symptoms such as scaly skin, hair loss or infertility to be signs of EFA deficiency and add B6 or animal fats to their diets. An excess of linoleate from vegetable oil will interfere with the production of DHA while an excess of EPA from fish oil will interfere with the production and utilization of AA. EFA are polyunsaturated fatty acids (PUFA) that contribute to oxidative stress. Vitamin E and other antioxidant nutrients cannot fully protect against oxidative stress induced by dietary PUFA.

Therefore, the consumption of EFA should be kept as close to the minimum requirement as is practical while still maintaining an appetizing and nutritious diet.

Purchase a subscription to a full volume, containing four reports, for $30 here or purchase the report singly below.

References

1. Anitschkow N, Experimental Arteriosclerosis in Animals. In: Cowdry EV, Arteriosclerosis: A Survey of the Problem. 1933; New York: Macmillan. pp. 271-322.

2. Cheng D. Prevalence, predisposition and prevention of type II diabetes. Nutrition & Metabolism. 2005;2:29.

3. Lehto S, Niskanen L, Suhonen M, Ronnemaa T, Laakso M. Medial Artery Calcification. A Neglected Harbinger of Cardiovascular Complications in Non-Insulin-Dependent Diabetes Mellitus. Arteriosis, Thrombosis, and Vascular Biology. 1996;16:978.

4. Steinberg D, The Cholesterol Wars: The Skeptics vs. The Preponderance of the Evidence.2000; San Diego: Academic Press.

5. Libby P. The molecular mechanisms of the thrombotic complications of atherosclerosis. J Intern Med. 2008;263(5):517-27.

6. Libby P. Inflammation and cardiovascular disease mechanisms. Am J Clin Nutr. 2006;83(suppl):456S-60S.

7. Tontonoz P, Nagy L, Alvarez JG, Thomazy VA, Evans RM. PPARgamma promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell. 1998;93(2):241-52.

8. Laufs U, Fata VL, Plutzky J, Liao JK. Upregulation of Endotelial Nitric Oxide Synthase by HMG CoA Reductase Inhibitors. Circulation. 1998;97:1129-1135.

9. Austin MA, Breslow JL, Hennekens CH, Buring JE, Willet WC, Krauss RM. Low-density lipoprotein sublass patterns and risk of myocardial infarction. JAMA 1988;260(13):1917-21.

10. Tribble DL, Holl LG, Wood PD, Krauss RM. Variations in oxidative susceptibility among six low density lipoprotein subfractions of differing density and particle size. Atherosclerosis. 1992;93:189-99.

11. Camejo G, Hurt-Camejo E, Wiklund O, Bondjers G. Association of apo B lipoproteins with arterial proteoglycans: Pathological significance and molecular basis. Atherosclerosis 1998;139:205-222.

12. Bergmark C, Dewan A, Orsoni A, Merki E, Miller ER, Shin M-J, et al. A Novel Function of Lipoprotein (a) as a Preferential Carrier of Oxidized Phospholipids in Human Plasma. J Lipid Res. 2008 Jul 3;[Epub ahead of print]

13. Henriksen T, Mahoney EM, Steinberg D. Enhanced macrophage degradation of low density lipoprotein previously incubated with cultured endothelial cells: Recognition by receptors for acetylated low density lipoproteins. Proc Natl Acad Sci USA. 1981;78(10):6499-6503.

14. de Rijke YB, Bredie SJH, Demacker PNM, Vogelaar JM, Hak-Lemmers HLM, Stalenhoef AFH. The Redox Status of Coenzyme Q10 in Total LDL as an Indicator of In Vivo Oxidative Modification. Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:127-133.

15. Nenseter MS, Drevon CA. Dietary polyunsaturates and peroxidation of low density lipoprotein. Curr Opin Lipidol. 1996;7(1):8-13.

16. Nagy L, Tontonoz P, Alvarez JG, Chen H, Evans RM. Oxidized LDL regulates macrophage gene expression through ligand activation of PPARgamma. Cell. 1998;93(2):229-40.

17. Mozaffarian D, Rimm EB, Herrington DM. Dietary fats, carbohydrate, and progression of coronary atherosclerosis in postmenopausal.

18. Conklin BS, Vito RP, Changyi C. Effect of Low Shear Stress on Permeability and Occludin Expression in Porcine Artery Endothelial Cells. World J Surg. 2007;31:733-43.

19. Tsimikas S, Brilakis ES, Miller ER, McConnell JP, Lennon RJ, Kornman KS, Witztum JL, Berger PB. Oxidized phospholipids, Lp(a) lipoprotein, and coronary artery disease. N Engl J Med. 2005;353(1):46-57.

20. Wang Z, Zou J, Cao K, Hsieh TC, Huang Y, Wu JM. Dealcoholized red wine containing known amounts of resveratrol suppresses atherosclerosis in hypercholesterolemic rabbits without affecting plasma lipid levels. Int J Mol Med. 2005;16(4):533-40.




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Web Tool to Check Heart Risk Is Doubted

By RONI CARYN RABIN
Published: September 20, 2010

It could hardly be simpler: go to the Web, pull up a point-system tool, plug in a few numbers and instantly calculate your chances of having a heart attack over the next 10 years.

Multimedia

Or not.

A new study finds that a widely used version of the ubiquitous heart attack risk calculator is flawed, misclassifying 15 percent of patients who would use it — almost six million Americans, of whom almost four million are inappropriately shifted into higher-risk groups that are more likely to be treated with medication.

And while the tool is easy to use, the authors say, the original calculator on which it is based is equally user-friendly for anyone with a computer — and significantly more reliable.

“People were told that for clinical purposes either one of the formulas could be used, that they were interchangeable,” said the study’s senior author, Dr. Michael Steinman, an associate professor of medicine at San Francisco Veterans Affairs Medical Center and the University of California, San Francisco. “Our study highlights that there can be meaningful differences for individual patients.”

The newer calculator was devised in 2001 as a simplified, pencil-and-paper version of a complicated mathematical formula developed from evidence accumulated over decades by a well-known epidemiological survey, the Framingham Heart Study, a joint project of Boston University and the National Heart, Lung and Blood Institute.

Both formulas require the same seven pieces of information: age, sex, total cholesterol, “good” HDL cholesterol, smoking status, systolic blood pressure and whether one takes drugs for hypertension.

The simplified system was developed so doctors and patients would not need a computer to calculate heart attack risk. Each risk factor corresponds to a number of points; the more points you have, the higher your risk of a heart attack.

Now that computers and hand-held electronic devices are all but universal, however, the original, more complicated formula is accessible to nearly everyone. Yet the simplified tool remains in broad use because it has been programmed into many Web sites and computer applications. And because most of these programs do not tell the user which method is being employed, it is impossible to tell the difference.

Among the sites that use the simplified tool are those of the American Heart Association, the Mayo Clinic and many drug companies.

The medical-software company Epocrates even uses it in specialized applications created for physicians for use on mobile devices to aid treatment decisions. (A spokeswoman said Epocrates used the points formula because physicians were more familiar with it).

The new study, published last month in The Journal of General Internal Medicine, suggests that the simplified system paints with too broad a brush.

Consider a hypothetical 45-year-old male smoker with total cholesterol of 179 and HDL of 38: he starts with 3 points for his age, adds 5 for smoking and 5 more for the cholesterol readings, for a total of 13 points — and a 12 percent chance of having a heart attack by age 55.

But under the original Framingham formula, his chance is actually just 7 percent, the study found. The discrepancy is significant, because cholesterol-lowering medicine is apt to be prescribed once a patient reaches a 10 percent risk.

The number of Americans potentially affected is in the millions. Ten percent of adults are shifted into higher-risk groups by the simplified system; at the same time, the system underestimates the risk for 5 percent of adults, who might benefit from more aggressive therapy. Women are disproportionately represented among the low-risk patients who are shifted into a higher-risk category.

“Even if it’s just a 5 percent difference of undertreatment versus overtreatment — why use a less accurate method?” said Dr. Kevin Fiscella, a professor of family and preventive medicine at the University of Rochester. “Especially when it’s quite easy to use a more accurate method with electronic devices.” Dr. Fiscella is a co-author of an editorial in the same journal about the study.

The risk calculator on americanheart.org, the heart association’s Web site, carries the logo of the Pharmaceutical Roundtable, a drug industry group, with a note that says, “The Pharmaceutical Roundtable is a proud sponsor of this risk calculator.”

In a telephone interview, Dr. Fiscella said he suspected the drug industry of promoting the less accurate method to expand the market share of patients who are eligible for cholesterol-lowering statin drugs.

“Let’s face it, the number of people is very high, in the millions, and from a pharmaceutical marketing perspective it does make a difference,” he said. “We have no data on whether they did their own internal analyses to determine which tool had a bigger impact on their market share or not, but it’s certainly conceivable. That’s the real world.”

A spokeswoman for the heart association said that it received funds from the Pharmaceutical Roundtable for the development of the risk assessment tool, but that “after the funding was committed, the PRT had no input whatsoever on the content.”

Dr. Daniel Levy, the director of the Framingham Heart Study at the National Heart, Lung, and Blood Institute, disputed the significance of the new paper, noting that the simplified formula produced results similar to the original one. “As you move from a point score to a continuous risk function, you’re moving to a more accurate assessment tool,” he said in an interview. “There’s no surprise there.

“It seems like much ado about nothing,” he added. “The two approaches were concordant 86 percent of the time.”

Experts note that the formulas are aimed at patients at intermediate risk of heart attack, and that people at very high risk — those with diabetes or a previous heart attack, for example — would not need a risk calculator to qualify for aggressive management.

Asked why the pen-and-paper formula had been embedded into computers, Dr. Levy said that people who do not own computers might use it in a public library and want to make a paper printout of the guidelines.

But Dr. Jesse Polansky of the federal Centers for Medicare and Medicaid Services, one of five authors of the study, called the simplified system “an antique.”

(Dr. Polansky, a former employee of Pfizer, is involved in a lawsuit asserting that the company promoted the formula to increase sales of its cholesterol-lowering drug Lipitor. He noted that the new study and his comments did not represent the Medicare centers’ views.)

“At the end of the day, patients and practitioners need to have the most accurate risk assessment available to them,” he said, “or we’re at greater risk for clinical misadventures.”



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Web Tool to Check Heart Risk Is Doubted

By RONI CARYN RABIN
Published: September 20, 2010

It could hardly be simpler: go to the Web, pull up a point-system tool, plug in a few numbers and instantly calculate your chances of having a heart attack over the next 10 years.

Multimedia

Or not.

A new study finds that a widely used version of the ubiquitous heart attack risk calculator is flawed, misclassifying 15 percent of patients who would use it — almost six million Americans, of whom almost four million are inappropriately shifted into higher-risk groups that are more likely to be treated with medication.

And while the tool is easy to use, the authors say, the original calculator on which it is based is equally user-friendly for anyone with a computer — and significantly more reliable.

“People were told that for clinical purposes either one of the formulas could be used, that they were interchangeable,” said the study’s senior author, Dr. Michael Steinman, an associate professor of medicine at San Francisco Veterans Affairs Medical Center and the University of California, San Francisco. “Our study highlights that there can be meaningful differences for individual patients.”

The newer calculator was devised in 2001 as a simplified, pencil-and-paper version of a complicated mathematical formula developed from evidence accumulated over decades by a well-known epidemiological survey, the Framingham Heart Study, a joint project of Boston University and the National Heart, Lung and Blood Institute.

Both formulas require the same seven pieces of information: age, sex, total cholesterol, “good” HDL cholesterol, smoking status, systolic blood pressure and whether one takes drugs for hypertension.

The simplified system was developed so doctors and patients would not need a computer to calculate heart attack risk. Each risk factor corresponds to a number of points; the more points you have, the higher your risk of a heart attack.

Now that computers and hand-held electronic devices are all but universal, however, the original, more complicated formula is accessible to nearly everyone. Yet the simplified tool remains in broad use because it has been programmed into many Web sites and computer applications. And because most of these programs do not tell the user which method is being employed, it is impossible to tell the difference.

Among the sites that use the simplified tool are those of the American Heart Association, the Mayo Clinic and many drug companies.

The medical-software company Epocrates even uses it in specialized applications created for physicians for use on mobile devices to aid treatment decisions. (A spokeswoman said Epocrates used the points formula because physicians were more familiar with it).

The new study, published last month in The Journal of General Internal Medicine, suggests that the simplified system paints with too broad a brush.

Consider a hypothetical 45-year-old male smoker with total cholesterol of 179 and HDL of 38: he starts with 3 points for his age, adds 5 for smoking and 5 more for the cholesterol readings, for a total of 13 points — and a 12 percent chance of having a heart attack by age 55.

But under the original Framingham formula, his chance is actually just 7 percent, the study found. The discrepancy is significant, because cholesterol-lowering medicine is apt to be prescribed once a patient reaches a 10 percent risk.

The number of Americans potentially affected is in the millions. Ten percent of adults are shifted into higher-risk groups by the simplified system; at the same time, the system underestimates the risk for 5 percent of adults, who might benefit from more aggressive therapy. Women are disproportionately represented among the low-risk patients who are shifted into a higher-risk category.

“Even if it’s just a 5 percent difference of undertreatment versus overtreatment — why use a less accurate method?” said Dr. Kevin Fiscella, a professor of family and preventive medicine at the University of Rochester. “Especially when it’s quite easy to use a more accurate method with electronic devices.” Dr. Fiscella is a co-author of an editorial in the same journal about the study.

The risk calculator on americanheart.org, the heart association’s Web site, carries the logo of the Pharmaceutical Roundtable, a drug industry group, with a note that says, “The Pharmaceutical Roundtable is a proud sponsor of this risk calculator.”

In a telephone interview, Dr. Fiscella said he suspected the drug industry of promoting the less accurate method to expand the market share of patients who are eligible for cholesterol-lowering statin drugs.

“Let’s face it, the number of people is very high, in the millions, and from a pharmaceutical marketing perspective it does make a difference,” he said. “We have no data on whether they did their own internal analyses to determine which tool had a bigger impact on their market share or not, but it’s certainly conceivable. That’s the real world.”

A spokeswoman for the heart association said that it received funds from the Pharmaceutical Roundtable for the development of the risk assessment tool, but that “after the funding was committed, the PRT had no input whatsoever on the content.”

Dr. Daniel Levy, the director of the Framingham Heart Study at the National Heart, Lung, and Blood Institute, disputed the significance of the new paper, noting that the simplified formula produced results similar to the original one. “As you move from a point score to a continuous risk function, you’re moving to a more accurate assessment tool,” he said in an interview. “There’s no surprise there.

“It seems like much ado about nothing,” he added. “The two approaches were concordant 86 percent of the time.”

Experts note that the formulas are aimed at patients at intermediate risk of heart attack, and that people at very high risk — those with diabetes or a previous heart attack, for example — would not need a risk calculator to qualify for aggressive management.

Asked why the pen-and-paper formula had been embedded into computers, Dr. Levy said that people who do not own computers might use it in a public library and want to make a paper printout of the guidelines.

But Dr. Jesse Polansky of the federal Centers for Medicare and Medicaid Services, one of five authors of the study, called the simplified system “an antique.”

(Dr. Polansky, a former employee of Pfizer, is involved in a lawsuit asserting that the company promoted the formula to increase sales of its cholesterol-lowering drug Lipitor. He noted that the new study and his comments did not represent the Medicare centers’ views.)

“At the end of the day, patients and practitioners need to have the most accurate risk assessment available to them,” he said, “or we’re at greater risk for clinical misadventures.”



XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX

Web Tool to Check Heart Risk Is Doubted

By RONI CARYN RABIN
Published: September 20, 2010

It could hardly be simpler: go to the Web, pull up a point-system tool, plug in a few numbers and instantly calculate your chances of having a heart attack over the next 10 years.

Multimedia

Or not.

A new study finds that a widely used version of the ubiquitous heart attack risk calculator is flawed, misclassifying 15 percent of patients who would use it — almost six million Americans, of whom almost four million are inappropriately shifted into higher-risk groups that are more likely to be treated with medication.

And while the tool is easy to use, the authors say, the original calculator on which it is based is equally user-friendly for anyone with a computer — and significantly more reliable.

“People were told that for clinical purposes either one of the formulas could be used, that they were interchangeable,” said the study’s senior author, Dr. Michael Steinman, an associate professor of medicine at San Francisco Veterans Affairs Medical Center and the University of California, San Francisco. “Our study highlights that there can be meaningful differences for individual patients.”

The newer calculator was devised in 2001 as a simplified, pencil-and-paper version of a complicated mathematical formula developed from evidence accumulated over decades by a well-known epidemiological survey, the Framingham Heart Study, a joint project of Boston University and the National Heart, Lung and Blood Institute.

Both formulas require the same seven pieces of information: age, sex, total cholesterol, “good” HDL cholesterol, smoking status, systolic blood pressure and whether one takes drugs for hypertension.

The simplified system was developed so doctors and patients would not need a computer to calculate heart attack risk. Each risk factor corresponds to a number of points; the more points you have, the higher your risk of a heart attack.

Now that computers and hand-held electronic devices are all but universal, however, the original, more complicated formula is accessible to nearly everyone. Yet the simplified tool remains in broad use because it has been programmed into many Web sites and computer applications. And because most of these programs do not tell the user which method is being employed, it is impossible to tell the difference.

Among the sites that use the simplified tool are those of the American Heart Association, the Mayo Clinic and many drug companies.

The medical-software company Epocrates even uses it in specialized applications created for physicians for use on mobile devices to aid treatment decisions. (A spokeswoman said Epocrates used the points formula because physicians were more familiar with it).

The new study, published last month in The Journal of General Internal Medicine, suggests that the simplified system paints with too broad a brush.

Consider a hypothetical 45-year-old male smoker with total cholesterol of 179 and HDL of 38: he starts with 3 points for his age, adds 5 for smoking and 5 more for the cholesterol readings, for a total of 13 points — and a 12 percent chance of having a heart attack by age 55.

But under the original Framingham formula, his chance is actually just 7 percent, the study found. The discrepancy is significant, because cholesterol-lowering medicine is apt to be prescribed once a patient reaches a 10 percent risk.

The number of Americans potentially affected is in the millions. Ten percent of adults are shifted into higher-risk groups by the simplified system; at the same time, the system underestimates the risk for 5 percent of adults, who might benefit from more aggressive therapy. Women are disproportionately represented among the low-risk patients who are shifted into a higher-risk category.

“Even if it’s just a 5 percent difference of undertreatment versus overtreatment — why use a less accurate method?” said Dr. Kevin Fiscella, a professor of family and preventive medicine at the University of Rochester. “Especially when it’s quite easy to use a more accurate method with electronic devices.” Dr. Fiscella is a co-author of an editorial in the same journal about the study.

The risk calculator on americanheart.org, the heart association’s Web site, carries the logo of the Pharmaceutical Roundtable, a drug industry group, with a note that says, “The Pharmaceutical Roundtable is a proud sponsor of this risk calculator.”

In a telephone interview, Dr. Fiscella said he suspected the drug industry of promoting the less accurate method to expand the market share of patients who are eligible for cholesterol-lowering statin drugs.

“Let’s face it, the number of people is very high, in the millions, and from a pharmaceutical marketing perspective it does make a difference,” he said. “We have no data on whether they did their own internal analyses to determine which tool had a bigger impact on their market share or not, but it’s certainly conceivable. That’s the real world.”

A spokeswoman for the heart association said that it received funds from the Pharmaceutical Roundtable for the development of the risk assessment tool, but that “after the funding was committed, the PRT had no input whatsoever on the content.”

Dr. Daniel Levy, the director of the Framingham Heart Study at the National Heart, Lung, and Blood Institute, disputed the significance of the new paper, noting that the simplified formula produced results similar to the original one. “As you move from a point score to a continuous risk function, you’re moving to a more accurate assessment tool,” he said in an interview. “There’s no surprise there.

“It seems like much ado about nothing,” he added. “The two approaches were concordant 86 percent of the time.”

Experts note that the formulas are aimed at patients at intermediate risk of heart attack, and that people at very high risk — those with diabetes or a previous heart attack, for example — would not need a risk calculator to qualify for aggressive management.

Asked why the pen-and-paper formula had been embedded into computers, Dr. Levy said that people who do not own computers might use it in a public library and want to make a paper printout of the guidelines.

But Dr. Jesse Polansky of the federal Centers for Medicare and Medicaid Services, one of five authors of the study, called the simplified system “an antique.”

(Dr. Polansky, a former employee of Pfizer, is involved in a lawsuit asserting that the company promoted the formula to increase sales of its cholesterol-lowering drug Lipitor. He noted that the new study and his comments did not represent the Medicare centers’ views.)

“At the end of the day, patients and practitioners need to have the most accurate risk assessment available to them,” he said, “or we’re at greater risk for clinical misadventures.”



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Framingham Slides










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Lipid researcher, 98, reports on the causes of heart disease

feature image
Photo by
L. Brian Stauffer

Fred Kummerow, a 98-year-old emeritus professor of comparative biosciences at the University of Illinois, explains the primary causes of heart disease. His research contradicts commonly held notions about the role of dietary cholesterol.

« Click photo to enlarge

Story
Email
2/27/2013 | Diana Yates, Life Sciences Editor | 217-333-5802; diya@illinois.edu

CHAMPAIGN, lll. — A 98-year-old researcher argues that, contrary to decades of clinical assumptions and advice to patients, dietary cholesterol is good for your heart – unless that cholesterol is unnaturally oxidized (by frying foods in reused oil, eating lots of polyunsaturated fats or smoking).

The researcher, Fred Kummerow, an emeritus professor of comparative biosciences at the University of Illinois, has spent more than six decades studying the dietary factors that contribute to heart disease. In a new paper in the American Journal of Cardiovascular Disease, he reviews the research on lipid metabolism and heart disease with a focus on the consumption of oxidized cholesterol – in his view a primary contributor to heart disease.

“Oxidized lipids contribute to heart disease both by increasing deposition of calcium on the arterial wall, a major hallmark of atherosclerosis, and by interrupting blood flow, a major contributor to heart attack and sudden death,” Kummerow wrote in the review.

Over his 60-plus-year career, Kummerow has painstakingly collected and analyzed the findings that together reveal the underlying mechanisms linking oxidized cholesterol (and trans fats) to heart disease.

Many of Kummerow’s insights come from his relentless focus on the physical and biochemical changes that occur in the arteries of people with heart disease. For example, he has worked with surgeons to retrieve and examine the arteries of people suffering from heart disease, and has compared his findings with those obtained in animal experiments.

He and his colleagues first reported in 2001 that the arteries of people who had had bypass operations contained elevated levels of sphingomyelin (SFING-oh-my-uh-lin), one of several phospholipids (phosphate-containing lipids) that make up the membranes of all cells. The bypass patients also had significantly more oxidized cholesterols (oxysterols) in their plasma and tissues than people who had not been diagnosed with heart disease.

Human cells incubated with the blood plasma of the cardiac patients also picked up significantly more calcium from the culture medium than cells incubated in the plasma of healthy patients. When the researchers added oxysterols to the healthy plasma, the proportion of sphingomyelin in the cells increased, as did the uptake of calcium.

Earlier research, including studies conducted by medical pioneer Michael DeBakey, noted that the most problematic plaques in patients with heart disease occurred at the branch-points of the arteries of the heart. Kummerow followed up on these reports by looking at the phospholipid content of the arterial walls in pigs and humans. He found (and reported in 1994) that the branch points of the arteries in humans and in swine also had significantly more sphingomyelin than other regions of the same arteries.

For Kummerow, the increase in sphingomyelin was a prime suspect in the blocked and calcified arteries of the cardiac patients. He had already found that the arteries of the newborn human placenta contained only about 10 percent sphingomyelin and 50 percent phosphatidylcholine (FOSS-fuh-tih-dul-COH-lean), another important phospholipid component of cell membranes.

“But when we looked at the arteries of people who had had bypass operations, we found up to 40 percent sphingomyelin and about 27 percent phosphatidylcholine,” Kummerow said. “It took us many more years to discover that when you added large amounts of oxysterols to the cells, then the phosphatidylcholine changed to sphingomyelin.”

Further evidence supported sphingomyelin’s starring role in atherosclerosis. When Kummerow and his colleagues compared the blocked and unblocked arteries of patients needing second bypass operations, they found that the arteries with blockages contained twice as much sphingomyelin as the unblocked arteries. The calcium content of the blocked arteries (6,345 parts per million) was also much higher than that of the unblocked arteries (182 ppm).

Other studies had demonstrated a link between increases in sphingomyelin and the deposit of calcium in the coronary arteries. The mechanism by which this occurred was unclear, however. Kummerow’s team searched the literature and found a 1967 study that showed that in the presence of certain salts (in the blood, for example), lipids like sphingomyelin develop a negative charge. This explains the attraction of the positively charged calcium to the arterial wall when high amounts of sphingomyelin are present, Kummerow said.

“So there was a negative charge on the wall of this artery, and it attracted calcium from the blood until it calcified the whole artery,” he said.

Oxidized fats contribute to heart disease (and sudden death from heart attacks) in an additional way, Kummerow said. He and his collaborators found that when the low-density lipoprotein (LDL, the so-called “bad cholesterol”) is oxidized, it increases the synthesis of a blood-clotting agent, called thromboxane, in the platelets.

If someone eats a diet rich in oxysterols and trans fats and also smokes, he or she is endangering the heart in three distinct ways, Kummerow said. The oxysterols enhance calcification of the arteries and promote the synthesis of a clotting agent. And the trans fats and cigarette smoke interfere with the production of a compound, prostacyclin, which normally keeps the blood fluid.

“And that causes 600,000 deaths in this country each year,” Kummerow said.

Kummerow is the author of “Cholesterol Won’t Kill You, But Trans Fats Could.”

Editor's note: To contact Fred Kummerow, call 217-344-6380.

The paper, “Interaction Between Sphingomyelin and Oxysterols Contributes to Atherosclerosis and Sudden Death,” is available online or from the U. of I. News Bureau.



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Foods High in Cholesterol Could Save Your Health.

July, 2005 Revised March, 2007

by Chris Masterjohn

No, you read that right. Foods high in cholesterol can actually save your health.

Cholesterol has been one of the most maligned and misunderstood substances of the twentieth century. Eating foods high in cholesterol was long thought to raise blood cholesterol levels, something considered to be so dangerous that some of the most nutritious foods on the planet -- like liver and egg yolks -- were demonized as enemies of our arteries.

Unfortunately the campaign against cholesterol has washed away from our daily menus many of the most important foods we should treasure for excellent health and vitality.

Polyunsaturated Fat — Healthy or Harmful?

Not only that, but medical researchers began recommending the consumption of vegetable oils to obtain large amounts of polyunsaturated fatty acids (PUFA), because these fatty acids reduce cholesterol levels. More recently, to counteract the negative effects of omega-6 PUFA from vegetable oils, many are recommending consuming high amounts of omega-3 PUFA from fish oils. But the need for PUFA is incredibly small and both omega-6 and omega-3 PUFA can contribute to degenerative disease by increasing exposure to "oxidative stress." For more information on the true requirement for PUFA, click here.

The Effect of Foods on Cholesterol Levels

Since we cannot possibly eat enough cholesterol to use for our bodies' daily functions, our bodies make their own. When we eat more foods rich in this compound, our bodies make less. If we deprive ourselves of foods high in cholesterol -- such as eggs, butter, and liver — our body revs up its cholesterol synthesis. The end result is that, for most of us, eating foods high in cholesterol has very little impact on our blood cholesterol levels.

In seventy percent of the population, foods rich in cholesterol such as eggs cause only a subtle increase in cholesterol levels or none at all. In the other thirty percent, these foods do cause a rise in blood cholesterol levels. Despite this, research has never established any clear relationship between the consumption of dietary cholesterol and the risk for heart disease.1 (See: Myth: Eating Cholesterol-Rich Foods Raises Blood Cholesterol Levels.)

Raising cholesterol levels is not necessarily a bad thing either. In fact, in one to three percent of the population, dietary cholesterol might be an essential nutrient.

Arachidonic Acid is Essential to Growth as Well as Healthy Hair and Skin

Moreover, cholesterol-rich foods are the main source of arachidonic acid (AA). While AA is often said to be inflammatory, it is actually the most critically essential fatty acid in the body. Healthy adults only need very little, if any, of it, but growing children, women who are looking to conceive or are pregnant or nursing, and people who are bodybuilding, suffering from degenerative diseases involving oxidative stress, or recovering from injury need to consume AA in the diet. Strict vegans and those who consume lots of omega-3 fats might also require AA in the diet. Signs of deficiency include scaly skin, hair loss, and infertility. Click here for more information on the requirement for arachidonic acid.

Which Foods are Highest In Cholesterol?

Below is a table that shows the top twenty cholesterol-rich whole foods from the USDA's database, listed by milligrams of cholesterol per gram of food. Although dietary cholesterol is not an essential nutrient for most people, the foods richest in cholesterol have unique nutrient profiles that make them critical components of a nutrient-dense diet. In order to maintain superb health, increased energy and stamina, peak mental performance, and sexual vitality, picking some of the foods at the top of this list for daily consumption will prove to be your best weapon.

Table 1: Top Twenty Foods High in Cholesterol

 

 

Food

Cholesterol Content by mass (mg/g)

Chicken Liver

5.61

Chicken Giblets

4.42

Eggs

4.24

Beef Liver

3.81

Turkey Giblets

2.89

Butter

2.18

Pork Liver Sausage

1.8

Shrimp

1.73

Sardines

1.42

Heavy Cream

1.4

Veal

1.34

Pork Ribs

1.21

Lamb

1.21

Turkey Neck

1.2

Pork Shoulder

1.14

Beef Chuck

1.05

Lard

0.94

Crab

0.89

Duck Meat

0.89

Salmon

0.87

 

 

Data taken from the USDA Nutrient Database for Standard Reference, Release 17. For a complete list of foods high in cholesterol that includes refined, enriched, and packaged foods, sorted by mg of cholesterol per serving, click on the underlined text. If you would like the same list of foods high in cholesterol sorted alphabetically, please click on the underlined text in this sentence.

Health Foods High in Cholesterol

Chicken liver takes the top-spot among all foods high in cholesterol, and the top seven contain three entries for liver. My must-read selection of articles on liver shows why liver should also take the top spot on your list of healthy foods to eat, why it knocks the socks off of any energy drink on the market, and how to find the right liver and prepare it correctly so you can actually enjoy it.

Everyone knows eggs - or, egg yolks, rather - are high in cholesterol. Many have, trying to maintain a "healthy" diet, discarded the yolks from this food for this reason.

My article on the Incredible, Edible Egg Yolk proves that this super-food contains nearly all the nutrition in an egg, and shows you how to find the healthiest eggs in your area.

The number six spot belongs to butter. Butter is an important part of a nutritious diet, that helps boost the immune system, and contains nutrients that build strong bones and teeth. Skim milk contains calcium, but it is the milk-fat in whole milk and butter that contains the nutrients that put that calcium where it needs to go.

Is Dietary Cholesterol an Essential Nutrient?

Choosing among the foods highest in cholesterol is important for two reasons. Not only are many of these foods true super-foods -- rich in a wide array of nutrients, many of which are difficult to find elsewhere -- but cholesterol itself may be an important dietary nutrient for at least one to three percent of the population and may be essential to their health.

Smith-Lemli-Opitz syndrome (SLOS) is a genetic condition arising from the inability to convert 7-dehydrocholesterol (a common precursor of both cholesterol and vitamin D) into cholesterol. Most often, it results in spontaneous abortion within the first sixteen weeks of gestation.2 Children who are born with the defect may suffer from mental retardation, autism, facial and skeletal malformations, visual dysfunctions and failure to thrive. The current treatment is dietary cholesterol.3

SLOS is an autosomal recessive disorder, which means that both parents must contribute a defective gene in order for their child to develop the disease. Thus only one in 60,000 infants are born with the disease.

The proportion of people who carry the SLOS gene, however, is much higher. Approximately one in a hundred North American Caucasians possess a copy of the defective gene, and as many as one in fifty or even one in thirty Central Europeans possess a copy of the defective gene.2 These people, called SLOS "carriers," have reduced cholesterol synthesis, but still synthesize enough cholesterol to escape the severe risks and abnormalities that characterize clinical SLOS. SLOS carriers, then, comprise from one percent to over three percent of many populations.

An important study published in the American Journal of Psychiatry in 20044 showed that people who carry the SLOS gene are more than three times as likely to have attempted suicide as those who do not carry the gene. Moreover, the methods of committing suicide among carriers of the SLOS gene were more violent: while the one suicide attempt among controls involved an overdose of over-the-counter diet pills, attempts among SLOS carriers involved not only diet pills and deliberate inhalation of exhaust fumes but also firearms and an attempt to crash a car.

This is consistent with studies showing that low blood cholesterol levels are associated with suicide and that cholesterol levels in certain areas of the brain are lower in those who commit suicide by violent means than in those who commit suicide by non-violent means.5

Unfortunately, this study of 105 subjects was not statistically powerful enough to conclusively determine that this association was not due to chance. It was powerful enough, however, to conclusively show that SLOS carriers were more than four times as likely to have at least one biological relative who attempted or committed suicide and almost six times as likely to have a first-degree relative who attempted or committed suicide.4

Dietary cholesterol decreases aggressive and self-injurious behaviors in patients with clinical SLOS. It also improves hyperactivity, irritability, attention span, muscle tone, endocrine function, resistance to infection, and gastrointestinal problems in these patients.3

Taken together, these data suggest that dietary cholesterol may be an essential nutrient for one to three percent of the population. Moreover, there may be other differences in genetics besides the SLOS gene that may contribute to reduced cholesterol synthesis and a requirement for dietary cholesterol in other people. Clearly, then, some people not only require the rich array of nutrients in cholesterol-rich foods but may even require the cholesterol itself.



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Lifespan:

MORE "ESSENTIAL" Fatty Acids Speed up Metabolism - But increase oxidative stress, descrease lifespan










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